1. Field of the Invention
The present invention is generally related to indole compounds. More specifically, the indole compounds are used as insecticides for control of Lepidoptera and Coleoptera species.
2. Background of the Art
Certain fungi produce specialized resting bodies known as sclerotia as a means for surviving adverse environmental conditions which other fungal bodies cannot tolerate, such as harsh climate, nutrient deficiency and desiccation. Generally, sclerotia remain viable in soil for periods of several years, and provide primary inoculum for the producing species when conditions again become favorable for fungal growth. Sclerotia are formed under natural conditions or in solid substrate fermentations, but are not commonly produced in the liquid fermentation cultures generally employed in studies of microbial metabolites. Accordingly, many novel sclerotial metabolites of common fungi such as Aspergillus have not been characterized.
While sclerotia are known to contain biologically active secondary metabolites not found in other fungal parts or in liquid cultures, study of sclerotia as sources of novel metabolites has been limited. Investigation of large sclerotia (ergots) of Claviceps purpurea led to the discovery and medicinal use of ergot alkaloids.
Sclerotia have recently been recognized as a valuable potential source for natural antiinsectans. Many sclerotia, which are subjected to predation by fungivorous insects and anthropods during their period of dormancy in soil, have been shown to contain metabolites that exert adverse physiological effects on insects. Gloer et al. [J. Org. Chem. 53: 5457 (1988)] and Wicklow et al. [Trans. Br. Mycol. Soc. 91: 433 (1988)] disclose the isolation of four antiinsectan aflavanine derivatives from the sclerotia of Aspergillus flavus for use in controlling the dried-fruit beetle Carpophilus hemipterus (Nitidulidae:Coleoptera). TePaske et al. [J. Org. Chem. 55: 5299 (1990)] disclose a related metabolite, aflavazole, which was isolated from extracts of A. flavus sclerotia. Gloer et al. [J. Org. Chem. 54: 2530 (1989)] describe an insecticidal indole diterpene known as nominine found only in the sclerotia of Aspergillus nomius for the control of the corn earworm Helicoperva zea (Lepidoptera), formerly Heliothis zea. Nominine is also disclosed by Dowd et al. in U.S. Pat. No. 5,017,598 issued May 21, 1991, and entitled "Nominine, an Insecticidal Fungal Metabolite".
The compounds penitrem A-F [de Jesus et al., J. Chem. Perkin Trans. I, 1847-1861 (1983)] and aflatrem [Gallagher et al., Tetrahedron Lett. 21: 239 (1980)] are known tremorgenic mycotoxins which are produced from strains of Penicillium crustosum and Aspergillus flavus, respectively. Paspalinine, paspalicine and paspaline from Claviceps paspali are also known to cause tremors in mice and domestic animals [Gallagher et al., Tetrahedron Lett. 21: 235 (1980); Springer and Clardy, Tetrahedron Lett. 21: 231 (1980)]. A mechanism of action for these tremorgens is proposed by Setala et al., Drug Chem. Toxicol. 12: 237 (1989).
Tremorgenic mycotoxins such as penitrem A, aflatrem and paspaline are described by Dowd et al. as possessing insecticidal activity [U.S. Pat. No. 4,973,601, issued Nov. 27, 1990; J. Antibiol. 41: 1868 (1988)] Dowd et al. disclose a method of controlling insects as H. zea and S. frugiperda by applying a fungal tremorgenic metabolite containing an indole moiety to a locus of insects.
There remains a continuing need for new insecticides because many agriculturally important insect species have developed a resistance to the most potent insecticides which are currently available. Moreover, environmentally tolerable replacements for these insecticides are declining. New natural, biodegradable insecticides which are relatively nontoxic to vertebrates and may be produced by fermentation processes are a cost effective replacement for known insecticides.